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Pharmacokinetics and Residue Depletion of Albendazole in Carp (Cyprinus Carpio)

Author: LinHong
Tutor: LuoYuLiang
School: Huazhong Agricultural University
Course: Aquaculture
Keywords: Reverse Phase High Performance Liquid Chromatography Residues Albendazole Albendazole sulfoxide Albendazole sulfone Albendazole aminosulfone Carp (Cyprinus Carpio) Pharmacokinetic
CLC: R96
Type: Master's thesis
Year: 2009
Downloads: 14
Quote: 1
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Abstract

A reversed-phase high performance liquid chromatographic（RP-HPLC） method was established in the experiment for the determination of albendazole（ABZ）,albendazole sulfoxide（ABZSO）,albendazole sulfone（ABZSO₂） and albendazole 2-aminosulfone （ABZSO₂NH₂） in plasma and tissue of Cyprinus Carpio.In this experiment,Varian325 series equipment and C₁₈ chromatography column was chosen;samples were twice extracted and purified with ethyl acetate,detected with UV at the wavelength 292 nm. And the mobile phase is constitutive of methanol,water and acetic acid（V/V/V,34/1/65）. In the range of 0.0625-32.0μg/mL,the linearity of its standard curve was excellent （Correlation coefficients were all over 0.999）,with the recoveries rate of ABZ、ABZSO、ABZSO₂ and ABZSO₂NH₂ all above 80.0%.In addition,the intra-day coefficient of variation ranged from 1.67%to 7.80%and the inter-day coefficient of variation ranged from 0.45%to 3.66%.Furthermore,the limit of detection（LOD） of ABZ、ABZSO、ABZSO₂ and ABZSO₂NH₂ in plasma、muscle、skin、kidney and liver were 0.02、0.03、0.05 and 0.05μg/mL;0.01、0.01、0.03 and 0.03μg/g;0.01、0.01、0.02 and 0.02μg/g;0.02、0.02、0.04 and 0.04μg/g;0.02、0.03、0.05 and 0.05μg/g;and the limit of quantitation （LOQ） of ABZ、ABZSO、ABZSO₂ and ABZSO₂NH₂ in plasma、muscle、skin、kidney and liver were all 0.0625μg/mL（μg/g）.In summary,the limit of detection（LOD） and limit of quantitation（LOQ） are both within the experimental requirements.This method is easy,rapid,high recovery rate with good reproducibility.The pharmacokinetics and metabolism of ABZ and its three principal metabolites were demonstrated following oral treatment in carp at water temperature of 20±2℃. ABZ was given to carp at a dosage of 10mg/kg body weight.The concentration-time data of ABZ、ABZSO、ABZSO₂ and ABZSO₂NH₂ in plasma after single oral administration in healthy Cyprinus Carpio were fitted to use a one-compartment model with first-order absorption.The main pharmacokinetic parameters,including the absorption rate constant （K_α）、the elimination half-life(t_1/2ke)、the area under the concentration-time curve（AUC）、the distribution volume（V_d/F）、the time-point of maximum concentration of the drug（T_p） and the maximum concentration(C_max) were 0.21、0.13、0.09 and 0.12h^-1;6.35、16.1、 16.30 and 11.94h;5.99、42.14、32.73 and 12.36μg·mL^-1·h;15.3、5.51、5.86 and 13.94L/kg;6.57、12.92、14.68 and 12.48h;0.32、1.04、0.79 and 0.35μg/mL,respectively.Moreover,the metabolism and depletion of ABZ and its metabolites was studied in muscle tissue with adhering skin in carp.ABZ was given to carp following oral administration at a dosage of 10 mg/kg body weight.Once a day,for 3 consecutive days. Muscle tissue with adhering skin sample were collected at 3,5,7,12,18,24,36,48,72, 96,120 and 144 h periods after the last dosage time.The results of the studies showed that:At 20±2℃water temperature,ABZ was full out absorpted most quickly;ABZSO and ABZSO₂ were effective for the long-term maintenance at a high concentration in muscle tissue with adhering skin;the concentration quantity of ABZSO₂NH₂ was the lowest and the elimination rate was lower.Based on the results of the residue depletion study,to ensure tissues samples are safe for consumption,it is suggested that the withdrawal periods should not less than 5 days at 20±2℃water temperature.

Pharmacokinetics and Residue Depletion of Albendazole in Carp (Cyprinus Carpio)

Abstract

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